Project Summary The Zika virus is known to be neurotropic. Animal studies show that the virus affects neural progenitor cells. Recent studies in rhesus monkeys suggest the Zika virus may persist in the central nervous system. Clinically, the effect of the Zika virus on the developing brain is well known, but the long-term consequences of Zika infection in the adult brain are not. Infected adults may have minor, or no, signs and symptoms during acute infection, but they may have long-term CNS consequences. One manifestation of central nervous system damage can be problems with central auditory processing. Our preliminary data from Brazil show an unexpectedly high rate of central auditory deficits in a small sample of young, Zika-infected mothers. Processing auditory information is a neurologically demanding task involving neural pathways throughout the brainstem and into the cortex. High-level linguistic and cognitive systems are also engaged. Our previous work has shown that chronic HIV infection can lead to persistent central auditory processing deficits that correlate with cognitive function. These deficits can also be seen with traumatic brain injury, mild cognitive impairment, and early Alzheimer?s disease. The present study will use tests of central auditory function (speech-in-noise, triple-digit, gap detection, duration pattern, frequency-following response) to determine if these results can be confirmed in a larger cohort of adults with a past history of a documented, symptomatic Zika infection. The results from those with a history of Zika infection will be compared with results from age, gender, and socioeconomic-status-matched cases without evidence of prior infection. We hypothesize that prior Zika infection will be associated with worse performance on central auditory tests on average. If true, this would describe a new and previously unknown central nervous system consequence of Zika infection and would indicate that long-term central nervous system consequences of Zika infection may be more widespread than previously thought. This could affect clinical practice since it would indicate that aggressive prevention efforts may need to move beyond pregnant women. It could also lead to the use of central hearing tests to screen individuals for long-term Zika effects. These tests can be short and easy to perform (speech-in-noise) or can be done without any subjective subject input (frequency-following response). This study engages an international team with expertise in Zika infection effects on hearing (Leal, Muniz, Universidade Federal de Pernambuco), integrated hearing testing systems (Clavier, Creare LLC), and use of the frequency following response to assess the central processing of sound (Kraus, Northwestern). The Dartmouth team (Buckey) is experienced in assessing the central nervous system effects of viral infections from previous work evaluating HIV effects on both peripheral and central hearing in Dar es Salaam, Tanzania and Shanghai China. If our pilot findings are confirmed, this would indicate lasting CNS dysfunction may be a consequence of adult Zika infection, highlight the need for more investigation, and perhaps refocus prevention efforts.